REACTION RATE AND ORAL EFFECTIVENESS OF CERTAIN ADRENERGIC BLOCKING COMPOUNDS

In experiments carried out to develop an orally active beta-haloamine adren-ergic blocking agent (Fellows et at., 1954) no direct correlation between intra-venous and oral effectiveness was found. In vitro studies with sodium thiosulfate indicated that there was a marked difference in the rate of chemical reactivity between beta-bromo- and beta-chloroalkylamines. We therefore tested a series of six pairs of these analogs for correlation between oral potency and chemical reactivity in an effort to explain the earlier findings. METHOD. Intravenous adrenolytic potency was determined in cats anesthetized with pentobarbital sodium and prepared to record carotid blood pressure by means of a mercury manometer. One hour after injection of the adrenolytic agent into a femoral vein, the degree of blockade was determined by successive administration of four standard doses of 12.5, 50.0 and 500 microgm. total and 1000 microgm. per kgm. of body weight of epinephrine intravenously. The blood pressure was allowed to return to normal or stabilize at a new level between each injection. The amount of the adrenolytic agent which would consistently reverse all four doses of epinephrine was called the “paralyzing dose.